Comments on: FDA Warns About Zocor And Muscle Damage

By: industry insider

industry insider — Fri, 10 Jun 2011 23:28:29 +0000

Laurie, the overwhelming majority of hospitalizations for rhabdomyolysis are not due to statin drugs. They are due to extreme exertion, wherein skeletal muscles break down and release myoglobin into the bloodstram. The myoglobin clogs up the kidneys leading to renal insufficiency and renal failure in fatal cases.

The most recent example was the case of 13 players from the University of Iowa who were hospitalized with nonfatal rhabdomyolysis after an extreme workout. Statin-associated rhabdomyolysis is more of a diagnosis of exclusion after the more common causes have been ruled out.

http://abcnews.go.com/Health/university-iowa-football-players-hospitalized-muscle-condition/story?id=12780810

By: Laurie

Laurie — Fri, 10 Jun 2011 19:19:15 +0000

OII -
You are looking at the rate for fatalities. Obviously the incidence of hospitalized cases of rhabdo would be substantially higher.

By: original industry insider

original industry insider — Fri, 10 Jun 2011 19:05:25 +0000

Robert, the problem with statins and rhabdomyolysis is not that it is a long term effect but rather an extremely rare event in the first place. The incidence of fatal rhabdomyolysis associated with statin use is 0.15 cases/million prescriptions in the US. This means that 100 million scrips would have to be written to yield 15 fatal cases. Assuming 12 scrips/patient/year, this means that approximately 8.3 million patients would have to take a given statin for one year for those 15 cases to show up in the data. Even for the best crackerjack pharmacovigilance team that is still a very low incidence to try to detect.

http://www.medicine.ox.ac.uk/bandolier/booth/cardiac/statmusc.html

By: Robert Kramer

Robert Kramer — Fri, 10 Jun 2011 17:16:39 +0000

I have noticed a disturbing trend regarding drugs that seem to be pushed to market before the long-term effects can be fully discovered. I understand that this is more about the dosage amount than anything else but shouldn’t care be taken by physician’s and others to ensure that any serious side effects are discovered and addressed immediately. I just think that pharma companies are concerned about the bottom line and not the people involved.

By: patrons99

patrons99 — Thu, 25 Mar 2010 16:54:22 +0000

Vet - how do you reconcile the LRC-CPPT study results with those of the WHO Clofibrate Study where “unlike the LRC-CPPT, this decline [in the overall incidence of major ischemic heart disease events] was confined to nonfatal myocardial infarction, whereas the incidence of fatal heart attack was similar in both treatment and control groups. Of concern in this study [the WHO Clofibrate Study] was the increased incidence in all-cause mortality in the clofibrate group, which became more significant during a four-year posttrial followup.”

Also, see Table 4 - Other Cardiovascular Events, from the LRC-CPPT Study JAMA article, where there was apparently a 21% increased risk of definite or suspect atherothrombotic brain infarction.

Lastly, I wonder what effect, if any, clofibrate and cholestyramine treatment have on fat soluble vitamin levels, e.g. Vitamin D3 levels.

By: pharmavet

pharmavet — Mon, 22 Mar 2010 17:21:17 +0000

CV and Justice, I don’t think many on this board understand the lipid solubility issue and how it relates to ubiquinones, potential for rhabdo, etc. Perhaps a lesson here would help.

By: Justice in MI

Justice in MI — Mon, 22 Mar 2010 16:59:25 +0000

Thanks, CV. That’s what I was guessing. atorva and prava are different in terms of lipid solubility, so you have those two options with best track record otherwise.

By: CV MD

CV MD — Mon, 22 Mar 2010 15:21:01 +0000

JiM - IMO, combination of clear efficacy and cleanest safety, primarily based on absence of significant drug-drug interactions and lack of lipid solubility.

By: pharmavet

pharmavet — Mon, 22 Mar 2010 15:11:05 +0000

Doc, I think we’re on the same page here. Although cholestyramine (Questran, Colestipol) is a nasty drug to take, it’s advantage is that it does not act by pleiotropic mechanisms, as do the statins. That is why I cited LRC-CPPT trial above in order to show a direct link between LDL-C lowering and reduced mortality from coronary heart disease using a non-pleiotropic drug.

By: Doc

Doc — Mon, 22 Mar 2010 12:13:21 +0000

All on the LDL/statin debate,
My thoughts were never to defend statins in all situations, I would advocate that for no drug or class.

Pleiotropic mechanisms may be important, but there are really no large scale prospective studies to show that positive link (especially which of the 20+ mechanisms people think are beneficial, really are) , there are however several large scale studies showing clear benefit of lower LDL with statins. 4S, PROVE-IT, WOSCOPS, etc. These were not powered to specifically look at elderly or women, but the outcomes are fairly impressive in terms of CV event reduction in regards to LDL reduction with statins.

Do statins have problems? Yes, as does ASA or any other medication, but have they been of benefit to many patients? Yes.

Interesting note, I know many MDs that give co-Q 10 with statins, but mainly because they think it will be of benefit.

A personalixed approach as extolled above by CV MD is the rational way to treat any patient.